Abstract | AIMS: Our previous studies have shown that N-n-butyl haloperidol iodide (F(2)) can antagonize myocardial ischemia/reperfusion (I/R) injury by blocking intracellular Ca(2+) overload. The present study is to test the hypothesis that the protective effects of F(2) on myocardial I/R injury is mediated by downregulating Egr-1 expression. METHODS: RESULTS: Treatment with antisense Egr-1 ODN significantly reduced Egr-1 protein expression and attenuated injury of myocardial tissues and cells. Meanwhile, treatment with F(2) significantly inhibited the overexpression of Egr-1 mRNA and protein in myocardial tissues and cells. Consistent with downregulation of Egr-1 expression by F(2), inflammation and other damages were significantly relieved evidenced by the amelioration of hemodynamics, the reduction in myocardial MPO activity as well as the decrease in leakage of cTnI and release of TNF-alpha from cardiomyocyte. CONCLUSIONS: These results suggested that the overexpression of Egr-1 was causative in myocardial I/R or H/R injury, and F(2) could protect myocardial tissues and cells from I/R or H/R injury, which was largely due to the inhibition of Egr-1 overexpression.
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Authors | Yanmei Zhang, Ganggang Shi, Jinhong Zheng, Zhao Tang, Ping Gao, Yanqiu Lv, Fuxiao Guo, Qiangyong Jia |
Journal | Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology
(Cell Physiol Biochem)
Vol. 20
Issue 5
Pg. 639-48
( 2007)
ISSN: 1015-8987 [Print] Germany |
PMID | 17762190
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Copyright | Copyright (c) 2007 S. Karger AG, Basel. |
Chemical References |
- Early Growth Response Protein 1
- Egr1 protein, rat
- N-n-butyl haloperidol iodide
- Oligodeoxyribonucleotides
- RNA, Messenger
- Troponin I
- Tumor Necrosis Factor-alpha
- Malondialdehyde
- Peroxidase
- Haloperidol
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Topics |
- Animals
- Base Sequence
- Cells, Cultured
- Early Growth Response Protein 1
(genetics, metabolism)
- Gene Expression Regulation
(drug effects)
- Haloperidol
(analogs & derivatives, chemistry, pharmacology)
- Male
- Malondialdehyde
(metabolism)
- Molecular Structure
- Myocardial Reperfusion Injury
(genetics, metabolism, pathology)
- Myocytes, Cardiac
(drug effects, metabolism)
- Oligodeoxyribonucleotides
(genetics)
- Peroxidase
(metabolism)
- RNA, Messenger
(genetics)
- Rats
- Rats, Sprague-Dawley
- Troponin I
(metabolism)
- Tumor Necrosis Factor-alpha
(metabolism)
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